SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Using personal computers in a grid is permitting the in silico screening of millions of molecules to seek out potential inhibitors of agents that pose bioterror threats. Current projects are targeting anthrax and smallpox, but the approach has many attractions for investigating any known protein target and its inhibition.
The variola virus was the first biological agent to be used as a military weapon. It is considered as one of the main agents that could potentially be used in the context of bioterrorism. Smallpox was declared eradicated in 1980. So, in case of a confirmed or suspected case of smallpox, a deliberate, intentional origin must be considered. The early diagnosis of the first case is essential for initiating an epidemiological alert. All physicians should be well informed of the epidemiological, clinical, diagnostic, and therapeutic aspects of smallpox.
There is great concern that smallpox could be used for bioterrorism. The disease has a high mortality rate and can be spread by aerosols, and immunity in the population is low. Although an initial release of smallpox could infect a large number of people, secondary spread would likely be slow because of the long incubation period and the close contact required for transmission. Hospital personnel and household contacts are at the greatest risk of becoming infected. An outbreak of smallpox will be controlled through surveillance, containment, vaccination, and isolation of cases-the strategy used to eradicate the disease globally in 1978. Pre-exposure vaccination is recommended for hospital personnel likely to be exposed to smallpox while caring for patients during an outbreak.
This article presents a brief history of the use of biological agents in warfare and bioterrorism. Bacillus anthracis, smallpox virus, and Yersinia pestis, historically have been and currently are considered the most likely candidates for potential use under these circumstances. This article discusses the clinical syndromes these agents cause and the role of vaccines in protection against them.
Limitation of a bioterrorist anthrax attack will require rapid and accurate recognition of the earliest victims. To identify clinical characteristics of inhalational anthrax, we compared 47 historical cases (including 11 cases of bioterrorism-related anthrax) with 376 controls with community-acquired pneumonia or influenza-like illness. Nausea, vomiting, pallor or cyanosis, diaphoresis, altered mental status, and raised haematocrit were more frequently recorded in the inhalational anthrax cases than in either the community-acquired pneumonia or influenza-like illness controls. The most accurate predictor of anthrax was mediastinal widening or pleural effusion on a chest radiograph. This finding was 100% sensitive (95% CI 84.6-100.0) for inhalational anthrax, 71.8% specific (64.8-78.1) compared with community-acquired pneumonia, and 95.6% specific (90.0-98.5) compared with influenza-like illness. Our findings represent preliminary efforts toward identifying clinical predictors of inhalational anthrax.
When considering viruses of potential importance as tools for bioterrorism, several viruses in the Bunya- and Togaviridae families have been cited. Among those in the Bunyaviridae family are Rift Valley fever, Crimean-Congo hemorrhagic fever, hanta, and sandfly fever viruses, listed in order of priority. Those particularly considered in the Togaviridae family are Venezuelan, eastern and western equine encephalitis viruses. Factors affecting the selection of these viruses are the ability for them to induce a fatal or seriously incapacitating illness, their ease of cultivation in order to prepare large volumes, their relative infectivity in human patients, their ability to be transmitted by aerosol, and the lack of measures available for their control. Each factor is fully considered in this review. Vaccines for the control of infections induced by these viruses are in varying stages of development, with none universally accepted to date. Viruses in the Bunyaviridae family are generally sensitive to ribavirin, which has been recommended as an emergency therapy for infections by viruses in this family although has not yet been FDA-approved. Interferon and interferon inducers also significantly inhibit these virus infections in animal models. Against infections induced by viruses in the Togaviridae family, interferon-alpha would appear to currently be the most useful for therapy.
We propose to develop an integrated rapid, semiportable, prototype point microbial detection/identification system for clinical specimens that is also capable of differentiating microbial bioterrorism attacks from threats or hoaxes by defining the pathogen. The system utilizes "flash" extraction/analytical system capable of detection/identification of microbes from environmental and clinical matrices. The system couples demonstrated technologies to provide quantitative analysis of lipid biomarkers of microbes including spores in a system with near-single cell (amol/microl) sensitivity. Tandem mass spectrometry increases specificity by providing the molecular structure of neutral lipids, phospholipids, and derivatized spore-specific bacterial biomarker, 2,6-dipicolinic acid (DPA) as well as the lipopolysaccharide-amide-linked hydroxy-fatty acids (LPS-ALHFA) of Gram-negative bacteria. The extraction should take about an hour for each sample but multiple samples can be processed simultaneously.
Only a few years ago bioterrorism was considered a remote concern but few today are complacent about the possibility of biological agents being intentionally used to cause widespread panic, disruption, disease and death. By its very nature, the biological weapons threat - with its close links to naturally occurring infectious agents and disease - requires a different paradigm than that for conventional terrorism, military strikes or attacks caused by other weapons of mass destruction. This evolving threat presents the medical, public health and scientific communities (importantly including biotechnology) with a set of difficult and pressing challenges. This article provides a brief overview of the threat from biological weapons, the nature of a bioterrorist attack and some of the issues that need to be addressed if we are to make meaningful progress to prevent or contain this disturbing and potentially catastrophic danger.
The United States has not suffered significant psychosocial or medical consequences from the use of biological weapons within its territories. This has contributed to a "natural" state of denial at the community level. This denial could amplify the sense of crisis, anxiety, fear, chaos, and disorder that would accompany such a bioterrorist event. A key part of primary prevention involves counteracting this possibility before an incident occurs. Doing so will require realistic information regarding the bioterrorism threat followed by the development of a planned response and regular practice of that response. Unlike in natural disasters or other situations resulting in mass casualties, emergency department physicians or nurses and primary care physicians (working in concert with epidemiologic agencies), rather than police, firemen, or ambulance personnel, will be most likely to first identify the unfolding disaster associated with a biological attack. Like community leaders, this group of medical responders must be aware of its own susceptibility to mental health sequelae and performance decrement as the increasing demands of disaster response outpace the availability of necessary resources. A bioterrorist attack will necessitate treatment of casualties who experience neuropsychiatric symptoms and syndromes. Although symptoms may result from exposure to infection with specific biological agents, similar symptoms may result from the mere perception of exposure or arousal precipitated by fear of infection, disease, suffering, and death. Conservative use of psychotropic medications may reduce symptoms in exposed and uninfected individuals, as may cognitive-behavioral interventions. Clear, consistent, accessible, reliable, and redundant information (received from trusted sources) will diminish public uncertainty about the cause of symptoms that might otherwise prompt persons to seek unnecessary treatment. Training and preparation for contingencies experienced in an attack have the potential to enhance delivery of care. Initiating supportive social, psychotherapeutic, and psychopharmacologic treatments judiciously for symptoms and syndromes known to accompany the traumatic stress response can aid the efficient treatment of some patients and reduce long-term morbidity in affected individuals. Preventive strategies and planning must take into account the idea that specific groups within the population are at higher risk for psychiatric morbidity. First responders comprise one group at psychologic risk in this situation, and healthcare providers comprise another. These and other high-risk groups will benefit from the same supportive interventions developed for the community as a whole.
Certain viruses, such as those that cause smallpox and hemorrhagic fevers, have been identified as possible bioterrorism agents by the Centers for Disease Control and Prevention. They have been designated as potential threats because large quantities can be propagated in cell culture, they are transmissible as aerosols and, for the most part, there are only limited vaccine and pharmaceutical strategies for either prevention or treatment of established infection. An additional concern is the potential to genetically modify these agents to enhance virulence or promote resistance to vaccines or identified antivirals. Although the major impact of these agents is human illness, the release of zoonotic agents, such as the Nipah virus, would have consequences for both humans and animals because infected and noninfected animals might need to be sacrificed to control the spread of infection. Continued research is necessary to develop effective strategies to limit the impact of these biological threats.
The events of the autumn of 2001 in the United States made it clear that the spectre of the use of microorganisms to intentionally harm humans is a reality. The current strategy to control disease outbreaks caused by the intentional release of bacteria is to use antimicrobial agents, both therapeutically and prophylactically. However, multidrug-resistant strains of bacterial bioterrorism agents occur naturally or have been bio-engineered, indicating how vulnerable this strategy is.
Measures of effectiveness (MOEs) are defined as operationally quantifiable management tools that provide a means for measuring effectiveness, outcome, and performance. No clear MOEs exist for determining success or failure of the management of a bioterrorism response. This is especially critical because management requires a multi-agency and multi-disciplinary decision-making and evaluation process. It is suggested that the minimum MOEs required to operationally measure outcome must contain a measuring response capacity for: (1) real-time public health surveillance system; (2) full coverage health information system; (3) capacity to measure variance across management timelines; (4) demonstrated decline in mortality and morbidity; (5) control of transmission rates of communicable agents; and (6) resource distribution across the entire population.
INTRODUCTION: Evidence suggests that regular disaster exercises have beneficial effects on subsequent mock and actual disaster responses. The purpose of this report is to describe a multiple hospital, bioterrorism exercise, evaluated by independent observers who used an evaluation template. METHODS: The overall tabletop exercise design included participation from 23 Joint Commission Accreditation of Healthcare Organizations hospitals, four health departments, and a representative from one federal agency. The exercise was evaluated by trained exercise observers utilizing an independently prepared, evaluation protocol. RESULTS: All exercise sites successfully identified the bio-agent involved and answered after-exercise debriefing questions without much difficulty. Evaluations, in the form of an after-action report by the independent observers, commented upon the many limitations to the construct of the exercise. CONCLUSION: Having an independent observer group at the exercise appeared to provide a value-added benefit for capturing subjective information and data. However, these data were not in a form conducive to statistical analysis. Further work is needed to create an evaluation tool that would allow for statistical analysis so that exercises can be compared and improvements can be objective.
Francisella tularensis (FT), a zoonotic bacterium that causes tularemia, has received attention as a possible bioterrorism threat. We developed a PCR assay for use in fixed, processed tissues, which are safer to handle and allow archival testing. PCR analysis for a 211-bp fragment of the FT lipoprotein gene was performed on tissues from 16 cases of tularemia. In all, 14/15 cases with intact DNA (93%) were positive for FT by PCR. Frequent histologic findings in PCR-positive tissues included irregular microabscesses and granulomas in liver, spleen, kidney, and lymph nodes, and necrotizing pneumonia. Unusual cases featuring suppurative leptomeningitis and gastrointestinal ulcers were also seen. As this disease is endemic in North America, and has been identified as a potential bioterroristic threat, awareness of the clinicopathologic spectrum of disease and available detection methods is increasingly important. This PCR assay, the first designed for use in processed tissues, is an excellent method for diagnosis of tularemia.
Much progress has been made in recent years to strengthen local, state, national and international capacities to detect and respond to bioterrorism events and naturally occurring outbreaks of disease. New tools and systems are available to estimate the potential impact of a biological event and predict resource needs for effective response, enable earlier detection of an attack or outbreak, enhance diagnostic capacity and facilitate rapid intervention to mitigate the impact of an event on a community. These advances have required new approaches to preparedness, planning and surveillance, as well as new partnerships and collaborations across a range of disciplines. We examine some of these developments, discuss potential uses and limitations of these approaches, and identify priorities for the future.
Francisella tularensis is a highly infectious aerosolizable intracellular pathogen that is capable of causing a debilitating or fatal disease with doses as low as 25 colony-forming units. There is no licensed vaccine available. Since the 1950s there has been concern that F. tularensis could be used as a biological threat agent, and it has received renewed attention recently owing to concerns about bioterrorism. The International Conference on Tularaemia in 2003 attracted more than 200 delegates, twice the number of participants as previous meetings. This is a reflection of the increased funding of research on this pathogen, particularly in the United States.
AIM: This paper aims to explore the management structures and issues surrounding the United Kingdom (UK) health services' preparedness and ability to effectively deal with major incidents involving bioterrorism. BACKGROUND: Recent reports and expert opinion have suggested that the health service response to terrorist incidents involving weapons of mass destruction are insufficient and ill-prepared. KEY ISSUES: Lack of clear guidance and parity across the UK, poor targeting of information, inadequate and insufficient equipment, under-resourcing, and unsatisfactory training are key factors that contribute to a worrying state of frontline unpreparedness. CONCLUSIONS: Health service managers need to capitalize on the Government's current concern about the threat of a bioterrorist attack and ensure that their departments are sufficiently equipped, and that their personnel are adequately educated and trained, to deal with any such incident. Better guidance needs to be produced and distributed to front line healthcare workers.
Bioterrorism has become a potential diagnostic consideration in infectious diseases. This article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting. The characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed. Ebola vieus and smallpox are also discussed as potential bioterrorist-transmitted infections from the clinical and epidemiologic standpoint. In addition to the clinical features of the infectious diseases mentioned, the article discusses the infectious disease control and epidemiologic implications of these agents when employed as bioterrorist agents. The review concludes with suggestions for postexposure prophylaxis and therapy.